The impact of neo/adjuvant treatment choices on prognosis for surgically treated small-cell neuroendocrine carcinoma of the cervix.

Small-cell neuroendocrine carcinoma of the cervix (SCNCC) is a rare and aggressive tumor with a poor prognosis. Surgical resection followed by adjuvant therapy is the standard treatment for early-stage disease but the influence of different neo/adjuvant treatment approaches remains unclear. Retrospectively, we collected patients' characteristics and treatments in two medical centers. Disease status and survival outcomes were renewed through follow-up. Statistics analysis mainly included Kaplan-Meier methods for survival curve estimation, log-rank test for survival curve comparison, and Cox proportional hazards models for independent prognostic factors prediction. Finally, 51 patients treated by radical surgery between January 2010 and April 2020 were enrolled with a median age of 50 years (range: 32-68). 12 (23.5%) patients were at stage IIIC1 according to the International Federation of Gynecology and Obstetrics (FIGO) 2018 staging systems and the rest were at the early stage. The mean tumor size was 3.6±1.3 cm. Pathological examination found 24 cases with pure SCNCC and 27 cases with admixed SCCC. 29 (56.9%) patients had deep stromal infiltration and 19 (37.3%) patients had lymphovascular space invasion. 34 (66.7%) patients received neo/adjuvant chemotherapy and pelvic radiation was conducted in 41 (80.39%) patients with a median dose of 46 Gy (range: 40-50.4 Gy). The median follow-up time was 25.0 months. The median disease-free survival (DFS) time was 23.0 months. 27 (52.9%) patients developed distant metastasis and 14 (27.5%) experienced local failure. The median overall survival (OS) was 32.0 months. Univariate and multivariate analysis showed neoadjuvant chemotherapy as negative (HR=2.081, 95% CI 1.030-4.203, p=0.041) and adjuvant chemotherapy (HR=0.409, 95% CI 0.213-0.784, p=0.020) as positive independent prognostic factor for DFS. For OS, only lymph node metastasis was confirmed as an independent prognostic factor in both univariate analysis (HR=1.528, 95% CI 1.011-2.308, p=0.044) and multivariate analysis (HR=1.697, 95% CI 1.041-2.768, p=0.034). In conclusion, for surgically treated SCNCC, adjuvant chemotherapy showed a positive influence on DFS while neoadjuvant chemotherapy harmed DFS. OS was unaffected by either treatment choice.

Mixed small cell neuroendocrine carcinoma and squamous cell carcinoma covered by tubulovillous adenoma in the rectum: a case report and detailed molecular analyses.

BACKGROUND: Previously, only six cases of mixed neuroendocrine-non-neuroendocrine neoplasm (MiNENs) with squamous cell carcinoma (SCC) component have been described in the colorectum, and the molecular landscape of MiNENs is also poorly understood. Herein, we present a unique case in which the SCC developed as a component of a MiNEN in the rectum. CASE PRESENTATION: The patient was firstly diagnosed as rectal small cell neuroendocrine carcinoma (SCNEC) covered by tubulovillous adenoma, and then mixed SCNEC and SCC in the same site 6 months later. Representative samples from the three histologic subtypes were then sent for next-generation sequencing (NGS) separately. Multiple liver metastases occurred in the following month after the last surgery. The patient died of ketoacidosis 1 year after initial diagnosis of the tumor. CONCLUSION: This is the first report of this exceedingly rare tumor type to include NGS of the 3 separate morphological entities. Our findings may expedite the understanding of combined tumors in the colorectum.

Lymphadenectomy Benefits Small Cell Carcinoma of Ovary: A Population-Based Analysis.

Small cell carcinoma of the ovary (SCCO) is a rare type of ovarian cancer with high aggressiveness. The optimal treatment modality remains elusive. This study aims to comprehensively investigate the survival impact of clinical characteristics and treatments including lymphadenectomy in SCCO. A retrospective cohort study was performed and included patients from the Surveillance, Epidemiology, and End Results (SEER) database. Data collected included demographics, therapeutic details, and pathologic characteristics. Propensity-score matching analysis (PSM) was carried out to balance baseline variables between SCCO and non-SCCO. Cox regression, Kaplan-Meier, and stratified analyses were conducted before and after PSM. After filtering, 80 records on SCCO and 39,662 records on non-SSCO were obtained. Patients with SCCO were more prone to present unilateral tumor (57.6% and 85.0%, p < 0.001), larger tumor size (>15 cm: 9.5% and 32.5%; 10-15 cm: 13.2% vs. 22.5%, p < 0.001), younger age (59.1 ± 14.91 vs. 37.2 ± 19.05; p < 0.001), single status (17.0% vs. 45.0%; p < 0.001), single malignant tumor in a lifetime (76.1% vs. 87.5%; p = 0.0244), and pathologic grade IV diseases (14.5% vs. 40.0%; p < 0.001) compared with non-SCCO. After balancing the baseline clinical characteristics with a 1:4 ratio PSM, a total of matched 72 patients with SCCO and 254 patients with non-SCCO were identified. The survival rate of SCCO was distinctly inferior to non-SCCO, particularly in FIGO I, II, and III stages. Lymphadenectomy was performed in 37 (51.39%) SCCO patients, of whom 12 (32.43%) were found to have pathologically positive lymph nodes. Lymphadenectomy was linked to favorable overall survival in SCCO, particularly in the advanced stage, and was also an independent prognostic factor, whereas lymphadenectomy did not reveal an edge in matched non-SCCO. There was a pronounced survival benefit for SCCO when at least 10 or more nodes were resected. Lymphadenectomy in a non-stage-dependent way should be considered and deserves further clinical validation to promote the overall survival in SCCO.

Limited-stage small cell carcinoma of the esophagus treated with curative esophagectomy: A multicenter retrospective cohort study.

BACKGROUND: This study aimed to investigate the efficacy of surgery in the treatment of small cell carcinoma of the esophagus (SCCE) and explore potential prognostic factors. METHODS: We screened patients with SCCE who underwent esophagectomy from 2010 to 2018 at three institutes. Differences in survival were analyzed using the Kaplan-Meier method and log-rank test. The prognostic factors were identified using univariate and multivariate analyses. RESULTS: A total of 69 patients were included. Multivariate analysis showed that TNM stage (hazard ratio [HR]: 4.10, 95% confidence interval [CI]: 1.57-10.75, p = 0.004) and adjuvant therapy (HR: 0.28, 95% CI: 0.16-0.51, p < 0.001) were independent prognostic factors. Stage I, stage IIA, and stage IIB disease were merged into the surgery response disease (SRD), whereas stage III disease into the surgery nonresponse disease (SNRD). The SRD group had significantly improved survival compared to the SNRD group (HR: 0.33, 95% CI: 0.19-0.58, p < 0.001). In addition, adjuvant therapy increased survival benefit in the SNRD group (p < 0.001) but not in the SRD group (p = 0.061). CONCLUSIONS: Surgery alone appears to be adequate for disease control in the SRD group, whereas multimodality therapy was associated with improved survival in the SNRD group.

Complete resolution of paraneoplastic syndrome of inappropriate antidiuretic hormone secretion following thymic small-cell carcinoma thoracoscopic resection.

Thymic neuroendocrine tumours are rare anterior mediastinal neoplasms often associated with paraneoplastic syndromes. A patient presented with intractable hyponatraemia and a DOTATATE-avid mediastinal mass. Following medical optimization, she underwent thoracoscopic thymectomy with en bloc thymic small-cell carcinoma resection. Her symptoms resolved and her sodium levels normalized. In localized disease, curative-intent, minimally invasive thymic neuroendocrine tumour resection is safe and effective following preoperative staging and paraneoplastic syndrome management.

[Long-Term Survival after Surgical Resection for Small Cell Neuroendocrine Carcinoma of the Gallbladder].

A 60-year-old woman was not accompanied by any symptom. She had a gallstone which was identified 20 years prior. Ultrasonography performed by a local doctor revealed that the gallbladder was filled with small stones, and the patient was referred to our department for further examination and treatment for gallbladder stone. Tumor markers are elevated. Contrast- enhanced CT revealed gallbladder stones and thickening in the gallbladder body. PET-CT showed abnormal accumulation of FDG-PET with SUVmax 3.6 in the body of the gallbladder. With a diagnosis of gallbladder cancer, extended cholecystectomy and gallbladder bed resection with regional lymph node dissection were performed. The tumor was diagnosed histologically as small cell type neuroendocrine carcinoma of the gallbladder(pT2a[SS], pN0, pStage ⅡA; Japanese society of hepato-biliary-pancreatic surgery, the 7th edition). The postoperative course was uneventful. This patient has been followed up for 8 years without obvious signs of recurrence. R0 resection and lack of lymph node metastasis can allow long- term survival.

Data from small cell neuroendocrine carcinoma of the cervix: FIGO 2018 staging is more accurate than FIGO 2009.

OBJECTIVE: To compare the prognostic value of International Federation of Gynecology and Obstetrics (FIGO) 2009 and 2018 staging systems in surgical patients with small cell neuroendocrine carcinoma of the cervix (SCNEC). METHODS: We re-staged 64 surgical IB-IIA (FIGO 2009) SCNEC patients according to the FIGO 2018 system and refined stage IIIC of FIGO 2018 based on tumor local invasion. The prognostic factors were analyzed, and the advantages of FIGO 2018 were compared with 2009. RESULTS: The 5-year overall survival rate (OS) was 78.5% for stage I and 22.2% for stage II (FIGO 2009). In FIGO 2018, there was no difference between stage I and II, and the 5-year OS was 74.1%, 60.2%, and 0% for stage I/II, IIIC1, and IIIC2. After combining stage IIIC with the local invasion stage (T1 was limited to the cervix and vagina; T2 involved the parametrium; T3 involved the pelvic or abdominal cavity), the 5-year OS for stage IIICT1, IIICT2, and IIICT3 was 83.3%, 30.0%, and 0%, respectively. CONCLUSIONS: For stage II SCNEC patients, FIGO 2009 underestimated the prognosis, while FIGO 2018 was more accurate. For stage IIIC, FIGO 2018 might be more individualized and accurate after combining stage IIIC with tumor local invasion.

Preoperative Chemotherapy for Limited-stage Small Cell Carcinoma of the Esophagus.

BACKGROUND: The optimal treatment approach for limited-stage small cell carcinoma of the esophagus remains uncertain. This study aimed to evaluate the efficacy and safety of preoperative chemotherapy in combination with surgery vs upfront surgery in those patients. METHODS: From June 2001 to June 2015, a total of 280 patients with limited-stage small cell carcinoma of the esophagus were screened from 60 131 patients with esophageal cancer. Outcome analysis of those patients who underwent preoperative chemotherapy in combination with surgery or upfront surgery was conducted. The primary end point was overall survival, and secondary end points included progression-free survival and safety. RESULTS: Of the 280 patients, 200 were men (71.4%), the median age was 64 years (range, 42-75 years), 171 patients (61.1%) patients had preoperative chemotherapy in combination with surgery, and 109 patients (38.9%) underwent upfront surgery. A pathologic complete response rate of 8.8% was noted in patients who received preoperative chemotherapy. Compared with the upfront surgery group, the preoperative chemotherapy group had a better median overall survival (26.0 months vs 19.5 months, respectively; hazard ratio, 0.69; 95% CI, 0.51 to 0.92; P = .011) and a prolonged progression-free survival (16.0 months vs 13.0 months, respectively; hazard ratio, 0.75; 95% CI, 0.57 to 0.99; P = .039). Postoperative complications and peritreatment mortality were comparable between both groups. CONCLUSIONS: Compared with upfront surgery, preoperative chemotherapy in combination with surgery improves overall survival in patients with limited-stage small cell carcinoma of the esophagus.

A Retrospective Study of 52 Patients With Primary Small Cell Carcinoma of the Esophagus Treated With Radical Surgery.

BACKGROUND: Primary small cell carcinoma of the esophagus (SCCE) is a rare and extremely fatal disease. We aim to evaluate the efficacy of radical surgery for resectable SCCE and to explore potential prognostic factors. METHODS: We retrospectively reviewed 52 consecutive SCCE patients who underwent radical surgery from February 1993 to November 2014 at a single institution. The Kaplan-Meier estimator with log-rank test was used to assess overall survival (OS), disease-free survival (DFS) and median survival time. Univariate and multivariable analyses were used to evaluate prognostic factors through Cox proportional hazard regression model. RESULTS: Twenty-five (48.1%) patients were treated with surgery alone, whereas 27 (51.9%) patients underwent adjuvant therapy after surgery. The median OS time was 17.4 months (95% CI: 13.5-21.3). The median DFS time was 13.4 months (95% CI: 7.7-19.0). Patients whose tumors were located in the lower part of thoracic esophagus and the esophagogastric junction showed significantly better OS (27.0 vs. 13.2 months, P = 0.016) and DFS (27.0 vs. 11.3 months, P = 0.017) than those located in the upper and middle parts. Patients with N0 status experienced significantly better OS (21.4 vs. 11.6 months, P = 0.012) and DFS (21.4 vs. 8.6 months, P = 0.012) than those with N+ status. Patients whose tumor lengths were shorter than 5 cm had a better OS (17.4 vs. 5.7 months, P = 0.035) than those longer than 5 cm. Patients who underwent chemotherapy experienced a significantly improved OS (21.0 vs. 14.1 months, P = 0.032) compared to surgery alone. Multivariable analysis showed that lower tumor location, shorter tumor length, pN0 status and chemotherapy independently predicted better OS; lower tumor location and pN0 status independently predicted better DFS. CONCLUSIONS: Radical surgery in combination with chemotherapy has better outcomes than surgery alone for resectable SCCE. Higher tumor location, longer tumor length, lymph node metastasis and not undergoing chemotherapy independently predict worse prognoses.

[Surgery treatment and prognosis analysis of 129 small cell carcinoma of the esophagogastric junction].

Objective: To analysis the prognosis related factors of patients with small cell cancer of the esophagogastric junction treated by surgery. Methods: The clinicopathologic data of 129 patients with small cell cancer of the esophagogastric junction underwent surgery treatment in the Fourth Hospital of Hebei Medical University from January 2004 to December 2010 were retrospectively analyzed. Univariate survival survival was performed by Kaplan-Meier method and Log rank test. Multivariate survival was analyzed by using Cox proportional hazard model. Results: Radical surgery was performed in 123 patients, whereas other 6 cases were conducted palliative operation. The 5-year overall survival (OS) rate of this cohort was 21.0% and median survival time was 25.7 months. The 5-year progression free survival (PFS) rate of this cohort was 11.0% and median PFS time was 19.1 months. The univariate analysis result showed that operation manner, radical or not, tumor length, lymph node metastasis, TNM stage, intravascular cancer embolus surgical margin positive or not, the expression of Syn, comprehensive treatment and radiochemotherapy after progression were associated with the OS of these patients (P<0.05). Multivariate analysis result showed that lymph node metastasis, radiochemotherapy after progression were independent risk factors of OS (P<0.05). Univariate analysis result showed that operation manner, radical or not, tumor length, TNM stage, lymph node metastasis, intravascular cancer embolus, surgical margin positive or not, the expression of Syn, comprehensive treatment and radiochemotherapy after progression were associated with PFS (P<0.05). Multivariate analysis showed that lymph node metastasis and radiochemotherapy after progression were independent risk factors of PFS (P<0.05). Conclusions: The prognosis of small cell cancer of the esophagogastric junction patients remains poor. Lymph node metastasis and radiochemotherapy after progression are regarded as independent prognostic factors of these patients.